Testing Short-Course Radiation Versus Standard-Course Radiation for Soft Tissue Sarcomas That Need Surgery and Radiation

NCT07615049 | Not Yet Recruiting Phase 3 DMC

• 3 other identifiers: S2505NCI-2026-02587U10CA180888
• Study Type: interventional
• Target: 296
• Locations: 0 countries
• Sites: N/A

Brief Summary

This clinical trial compares the effect of short-course ultrahypofractionated radiation therapy over 5 days (UHRT-5) to standard-course radiation therapy over 25 days (RT-25) in treating patients with soft tissue sarcomas of the extremities that may be primary or that may have come back to nearby tissue or lymph nodes after a period of improvement (locally recurrent) and that can be removed by surgery (resectable). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. 3-dimensional (3D) conformal radiation therapy (CRT) uses a computer to create a 3D picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. Intensity-modulated radiation therapy (IMRT) is a type of 3D radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Standard-course (fractionated) radiation divides the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. Ultrahypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving UHRT-5 may be as effective as RT-25 in treating patients with primary or locally recurrent soft tissue sarcomas of the extremities that are resectable. It may also improve quality of life by requiring fewer treatments.

Conditions

Recurrent Soft Tissue Sarcoma of the Trunk and Extremities; Resectable Soft Tissue Sarcoma of the Trunk and Extremities; Soft Tissue Sarcoma of the Trunk and Extremities; Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8; Stage II Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8

Outcome Measures

Primary Outcomes (1)

• Local tumor recurrence rate

  Cumulative incidence of local tumor recurrence will be estimated non-parametrically with death from any cause analyzed as a competing risk. 2-year estimates of local tumor recurrence and standard errors will be calculated and used to calculate a one-sided 95% confidence internal for the difference in 2-year local tumor recurrence rates.

  At 2 years

Secondary Outcomes (6)

• Incidence of acute wound complications

  Up to 4 months after surgery

• Incidence of late-term complications associated with radiation

  Up to 2 years post-surgery

• Changes in physician-assessed functional outcome

  From pre-randomization up to 24 months post-surgery

• Overall survival

  From randomization up to 10 years

• Progression-free survival

  From randomization up to 10 years

Other Outcomes (5)

• Incidence of local tumor recurrence

  At 2 years

• Incidence of delayed wound healing

  Up to 6 months post-surgery

• Type of surgical resection

  At time of surgery

Study Arms (2)

Arm 1 (RT-25)

ACTIVE COMPARATOR

Patients undergo RT-25 with 3D CRT or IMRT QD for up to 5 fractions per week for 25 fractions over a minimum of 32 calendar days and maximum of 49 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo MRI, CT, and blood sample collection throughout the study.

Radiation: 3-Dimensional Conformal Radiation Therapy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Surgical Procedure

Arm 2 (UHRT-5)

EXPERIMENTAL

Patients undergo UHRT-5 with 3D CRT or IMRT QD for up to 5 fractions per week for 5 fractions over a minimum of 5 calendar days and maximum of 14 days in the absence of disease progression or unacceptable toxicity. Starting 22-56 calendar days after radiation, patients undergo surgical resection. Additionally, patients undergo MRI, CT, and blood sample collection throughout the study.

Radiation: 3-Dimensional Conformal Radiation Therapy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Procedure: Surgical Procedure

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm 1 (RT-25); Arm 2 (UHRT-5)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm 1 (RT-25); Arm 2 (UHRT-5)

Intensity-Modulated Radiation Therapy RADIATION

Undergo RT-25 with IMRT

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Arm 1 (RT-25)

Surgical Procedure PROCEDURE

Undergo surgical resection

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Arm 1 (RT-25); Arm 2 (UHRT-5)

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo RT-25 with 3D-CRT

Also known as: 3-dimensional radiation therapy, 3D Conformal, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D radiotherapy, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy, Radiation, 3D Conformal, Three dimensional external beam radiation therapy (procedure)

Arm 1 (RT-25)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (RT-25); Arm 2 (UHRT-5)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histological evidence of a soft tissue sarcoma from core or incisional biopsy. Participants must have a primary or locally recurrent tumor. Stage II-IIIB (by American Joint Committee on Cancer \[AJCC\] 8th edition) soft tissue sarcoma is required
• Prior partial excision or partial excisional biopsy of the tumor, with imaging evidence of gross residual disease \> 1cm in longest dimension (stage II-IIIB)
• Participants must have a primary site of disease in the extremity, including the shoulder girdle and hip girdle but excluding the hands and feet
• Participants with primary sites of trunk, head, neck, or intra-abdominal, intrapelvic, or retroperitoneal region are not eligible
• Participants with extension of the primary tumor into adjacent regions (e.g. torso, hands, feet) are eligible
• Participants must have an MRI of the primary site within 90 days prior to randomization. The MRI field of view must contain the entirety of the tumor (may be accomplished with multiple MRI scans). MRI must contain axial acquired T1 weighted with fat suppression, T1 weighted sequence with gadolinium contrast with fat suppression, and T2 weighted fat suppression sequence
• Participants must have no evidence of metastatic disease by CT imaging of the chest (or positron emission tomography \[PET\] CT), within 28 days before randomization
• Participants with pulmonary nodule(s) measuring 6-10 mm on chest CT are eligible if the nodules appear stable compared to prior chest imaging from at least 6 months ago, or if an fludeoxyglucose F-18 (18FDG)-PET scan indicates that the nodules are unlikely to be metastatic disease
• Pulmonary nodules \> 10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging
• Participants must not have fungating tumor. (i.e., tumor breakthrough of skin)
• Participants must not have myxoid liposarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, gastrointestinal stromal tumor, osteosarcoma, neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm, desmoplastic small round cell tumor, Ewing sarcoma, or sarcoma arising from bone
• Participants must not have known brain metastases. Brain imaging studies are not required for eligibility if the participant has no neurologic signs or symptoms suggestive of brain metastasis. If brain imaging studies are performed, they must be negative for disease
• Participants must have been evaluated by a surgeon, and it must have been determined that they are a good candidate for a limb salvage resection with an expectation of negative margins, within 35 days prior to randomization. Anticipated positive margins on fixed critical structures are allowed
• Participants must not have had prior treatment for the current tumor (systemic therapy, radiation, or complete surgical resection)
• Participants must not have had prior radiation to the anatomical site

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Interventions

Radiotherapy, Conformal; Specimen Handling; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jeremy P Harris

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 29, 2026
• Study Start (Estimated): December 2, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2030
• Last Updated: May 29, 2026

Record last verified: 2026-05